Aldh2 deficiency plays a dual role in lung tumorigenesis and tumor progression.
Aldh2 deficiency plays a dual role in lung tumorigenesis and tumor progression.
复制标题
Aldh2 缺乏在肺肿瘤发生和肿瘤进展中发挥双重作用。
DOI：
10.1016/j.gendis.2023.04.030
复制
发表时间：
2024-05
期刊：
影响因子：
6.8
通讯作者：
Deng, Jiong
中科院分区：
文献类型：
--
作者：
Zhang, Hongjia;Sun, Xueqian;Li, Zhanming;Liu, Tingting;Zhang, Fang;Meng, Xinyu;Li, Kaimi;Xu, Jianhua;He, Wei;Jing, Bo;Wangi, Tong;Ni, Na;Sun, Beibei;Yao, Feng;Wu, Yadi;Wang, Qi;Du, Jing;Chin, Eugene Y.;Zhou, Binhua P.;Jiang, Ping;Wang, Lishun;Deng, Jiong
酒精消费导致了全球死亡率和癌症的发展。乙醛(ACE)是乙醇的氧化代谢产物，与DNA高度反应，形成DNA加合物。血管紧张素转换酶可被乙醛脱氢酶2型(ALDH2)解毒为乙酸酯。ALDH2缺乏可导致ACE积聚和DNA损伤。1因此，ALDH2缺乏被认为是致癌的。2有趣的是，有超过5.4亿人携带ALDH2酶的多态。2∗是一种显性-负性变异体，显著降低了酶活性。这表明人类对ALDH2缺乏有很好的耐受性。令人惊讶的是，最近的一份流行病学报告显示，ALDH2纯合子的风险。2IARC酒精相关癌症和肺癌的∗携带者在男性中显著减少，而不是增加。3这是矛盾和令人困惑的，因为ACE或反应性氧化物种(ROS)是促癌的。为了研究ALDH2在肿瘤发生发展中的作用，我们在TIMER数据库中分析了正常组织和不同肿瘤组织中的ALDH2 mRNA。在大多数癌症中，ALDH2在肿瘤组织中的表达低于正常组织，包括肺腺癌(LUAD)和肺鳞状细胞癌(LUSC)。S1a)。此外，与I期相比，肿瘤IV期的ALDH2显著降低(P=0.0172)(图3)。S1B)。癌症基因组图谱(TCGA)的数据一致地表明，低ALDH2的LUAD患者的总体存活率显著短于ALDH2高的患者(P=0.0042)(图4)。S1C)。因此，ALDH2缺乏与肺癌的进展有关。
Alcohol consumption contributes to global mortality and cancer development. Acetaldehyde (ACE), the oxidized metabolite of alcohol, is highly reactive towards DNA, resulting in DNA adducts. ACE can be detoxified to acetate by acetaldehyde dehydrogenase type 2 (ALDH2). ALDH2 deficiency can lead to ACE accumulation and DNA damage. 1 Thus, ALDH2 deficiency is considered pro-oncogenic. 2 Interestingly, there are more than 540 million people carrying a polymorphism of the enzyme, ALDH2. 2∗ a dominant-negative variant that has substantially reduced enzymatic activity. This suggests that ALDH2 deficiency is well tolerated in humans. Surprisingly, a recent epidemiological report shows that the risk of homozygotes of ALDH2. 2∗ carriers for IARC alcohol-related cancer and lung cancer is significantly reduced, rather than increased, in men. 3 This is contradictory and perplexing since ACE or reactive oxidative species (ROS) is pro-oncogenic. However, there is no explanation.To investigate the roles of ALDH2 in cancer development, we analyzed ALDH2 mRNA in normal and tumor tissues of various cancers in the TIMER database. ALDH2 expression was low in tumor tissues compared to that in normal tissues for most cancers, including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC)(Fig. S1A). Moreover, ALDH2 was significantly reduced in tumor stage IV as compared to tumor stage I (P= 0.0172)(Fig. S1B). Consistently, The Cancer Genome Atlas (TCGA) data showed that the overall survival rate of LUAD patients with low ALDH2 was significantly shorter than those with high ALDH2 (P= 0.0042)(Fig. S1C). Thus, ALDH2 deficiency is associated with lung tumor progression.
登录
查看更多内容
影响因子：
11.2
作者：
Yin, Huijing;Jing, Bo;Deng, Jiong
通讯作者：
Deng, Jiong
影响因子：
6.4
作者：
Im PK;Yang L;Kartsonaki C;Chen Y;Guo Y;Du H;Lin K;Kerosi R;Hacker A;Liu J;Yu C;Lv J;Walters RG;Li L;Chen Z;Millwood IY;China Kadoorie Biobank (CKB) Collaborative Group
通讯作者：
China Kadoorie Biobank (CKB) Collaborative Group
影响因子：
64.8
作者：
Garaycoechea JI;Crossan GP;Langevin F;Mulderrig L;Louzada S;Yang F;Guilbaud G;Park N;Roerink S;Nik-Zainal S;Stratton MR;Patel KJ
通讯作者：
Patel KJ
影响因子：
10.3
作者：
Tao, Qingguo;Fujimoto, Junya;Lotan, Reuben
通讯作者：
Lotan, Reuben
ALDH2 抑制通过积累的乙醛和 DNA 损伤促进肺肿瘤进展
影响因子：
4.8
作者：
Li, Kaimi;Guo, Wenzheng;Deng, Jiong
通讯作者：
Deng, Jiong